Form Of Interstitial Lung Disease Research Articles

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Challenges in the management of idiopathic pulmonary fibrosis from a low- and middle-income country

Idiopathic pulmonary fibrosis (IPF) is the most common progressive form of interstitial lung disease (ILD) that leads to gradual deterioration of lung function and ultimately death. Data from low- and middle-income countries (LMIC) on IPF is scarce. In this communication, we report the challenges encountered in managing IPF from Pakistan’s largest tertiary care centre. A total of 108 patients with IPF were evaluated at the Aga Khan University Hospital in Karachi, Pakistan from January 2017 to March 2020. A significant concern was that most patients with IPF presented late during their disease. A bigger challenge encountered in clinical practice was the cost and non-availability of antifibrotic therapy in the country until mid-2020. Successfully addressing these limitations, it is anticipated that better care will be available for the patients suffering from IPF in this part of the world. Keywords: Interstitial Lung Disease, Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis, LMIC.

Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.

We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4709724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P=0.01), younger (mean age of 67.4 vs. 71.4; P<0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P<0.01), hyperlipidaemia (39.1% vs. 52.9%; P<0.01), diabetes (22.5% vs. 49.1%; P<0.01), obesity (13.2% vs. 25.0%; P<0.01), and hypertension (20.2% vs. 23.8%; P<0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P<0.01) and pulmonary hypertension (36.6% vs. 12.7%; P<0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P<0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P<0.01), Black (15.7% vs. 13.0%; P<0.01), and Hispanic (13.3% vs. 6.9%; P<0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P<0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P=0.02) and higher hospitalization costs ($67363 vs. $57128; AMD: 198.9; 95% CI: -4780 to 5178; P=0.93). In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors.

Hidden in Plain Sight: Pitfalls of a Case of Amyopathic Anti-Synthetase Syndrome Associated with Grawitz Tumor

Abstract Anti-synthetase syndrome (ASS) is a rare autoimmune disease whose hallmark consists of the presence of autoantibodies directed against aminoacyl transfer RNA (tRNA) synthetases thus making it a distinctive pathology of the broad spectrum of idiopathic inflammatory myopathies (IIM). Clinically, lung involvement in the form of interstitial lung disease (ILD) and myositis are typical findings. Inflammatory myopathies should always raise the suspicion of an adjancent tumoral process and therefore prompt the clinician to perform a thorough screening. We present the case of a 55 year old caucasian male who was diagnosed with amyopathic ASS and a clear cell renal carcinoma (Grawitz tumor), along with the consequent therapeutic challenges.

Phœnix dactylifera, L. seed oil alleviates Bleomycin-induced pulmonary fibrosis and oxidative stress in Wistar rats

Objective Idiopathic pulmonary fibrosis (IPF) is the most serious form of interstitial lung disease. We aimed to investigate the effect of Phœnix dactylifera, L. seed oil (DSO) on a murine model of IPF induced by bleomycin (BLM). Methods Male Wistar rats were treated with a single intra-tracheal injection of BLM (4 mg/kg) and a daily intraperitoneal injection of DSO (75, 150 and 300 mg/kg) for 4 weeks. Results Our phytochemical results showed that DSO has an important antioxidant activity with a high content of polyphenols and flavonoids. High-Performance Liquid Chromatography (HPLC) and Gas chromatography/mass spectrometry (GC-MS) analysis revealed a high amount of oleic and lauric acids and a large quantity of vitamins. Histological examination showed a significant reduction in fibrosis score and collagen bands in the group of rats treated with 75 mg/kg of DSO compared to the BLM group. DSO (75 mg/kg) reversed also the increase in catalase and malondialdehyde (MDA) levels while higher doses (150 and 300 mg/kg) are ineffective against the deleterious effects of BLM. We revealed also that DSO has no renal or hepatic cytotoxic effects. Conclusion DSO can play antioxidant and antifibrotic effects on rat models of pulmonary fibrosis at the lowest dose administered.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients

BackgroundIdiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients.MethodsFrom December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction.ResultsWe enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80–0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73–0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71–0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67–0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03–2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11–10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis.ConclusionThe clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Pleuro-Parenchymal Fibroelastosis (PPFE)-A Case Report

Pleuro-parenchymal fibroelastosis (PPFE) is a rare form of interstitial lung disease with pleural and parenchymal components in the form of fibrosis and elastosis. This is often missed due to its rarity and nonspecific symptoms. Most of the cases were attributed to trivial respiratory infections in the past. Here we present a case of an elderly female who is symptomatic after COVID-19 infection and has characteristic radiological patterns in high-resolution computed tomogram (HRCT) to suggest a diagnosis of PPFE.

Exploring the Role of Biomarkers Associated with Alveolar Damage and Dysfunction in Idiopathic Pulmonary Fibrosis-A Systematic Review.

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases (ILDs), marked by an ongoing, chronic fibrotic process within the lung tissue. IPF leads to an irreversible deterioration of lung function, ultimately resulting in an increased mortality rate. Therefore, the focus has shifted towards the biomarkers that might contribute to the early diagnosis, risk assessment, prognosis, and tracking of the treatment progress, including those associated with epithelial injury. We conducted this review through a systematic search of the relevant literature using established databases such as PubMed, Scopus, and Web of Science. Selected articles were assessed, with data extracted and synthesized to provide an overview of the current understanding of the existing biomarkers for IPF. Signs of epithelial cell damage hold promise as relevant biomarkers for IPF, consequently offering valuable support in its clinical care. Their global and standardized utilization remains limited due to a lack of comprehensive information of their implications in IPF. Recognizing the aggressive nature of IPF among interstitial lung diseases and its profound impact on lung function and mortality, the exploration of biomarkers becomes pivotal for early diagnosis, risk assessment, prognostic evaluation, and therapy monitoring.

99mTc-Labeled FAPI SPECT Imaging in Idiopathic Pulmonary Fibrosis: Preliminary Results.

Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis, presenting the most aggressive form of interstitial lung diseases (ILDs). Activated fibroblasts are crucial for pathological processes. Fibroblast activation protein (FAP) inhibitor (FAPI) tracers would be promising imaging agents for these diseases. The purpose of this study was to evaluate a 99mTc-labeled FAPI tracer, 99mTc-HFAPI imaging in IPF patients. Eleven IPF patients (nine males and two females; age range 55-75 year) were included in this pilot study. 99mTc-HFAPI serial whole-body scintigraphy at 5 min, 20 min, 40 min, 1 h, 2 h, 3 h, 4 h, and 6 h was acquired for dynamic biodistribution and dosimetry estimation in seven representative patients. SPECT/CT tomography fusion imaging of the chest region was performed in all patients at 4 h post-injection, which was considered as the optimal acquisition time. Dosimetry was calculated using OLINDA/EXM software (version 2.0; HERMES Medical Solutions). The quantified or semi-quantified standardized uptake values (SUVs) and lesion-to-background ratios (LBRs) of affected lung parenchyma were also calculated. The high-resolution CT (HRCT) stage was determined with visual evaluation, and the total HRCT score of each patient was measured using a weighting factor formula. Pulmonary function tests (PFTs) were recorded as well. Then, the relationships between the 99mTc-HFAPI results, disease extent on HRCT, and PFT results were investigated. Normal physiological uptake of 99mTc-HFAPI was observed mainly in the liver, intestinal tract, pancreas, gallbladder, and to a lesser extent in the spleen, kidneys, and thyroid, with no apparent retention in the blood circulation at the late time point. The mean injected activity of 99mTc-HFAPI was 813.4 MBq (range 695.6-888.0 MBq). No subjective side effects were noticed. The average whole-body effective dose was 0.0041 mSv/MBq per patient. IPF patients exhibited elevated pulmonary 99mTc-HFAPI uptake in abnormal lung regions, which was correlated with fibrotic regions on HRCT. Among different HRCT stage groups, both SUVmax and LBR showed significant differences (p < 0.001). The higher HRCT stage demonstrated significantly higher SUVmax and LBR. A linear correlation between 99mTc-HFAPI uptake and total HRCT score was observed for SUVmax (r = 0.7839, F = 54.41, p = 0.0094) and LBR (r = 0.7402, F = 56.33, p = 0.0092). 99mTc-HFAPI uptake also had moderate correlations with PFT results. Our preliminary data show that the 99mTc-HFAPI SPECT imaging is a promising new imaging modality in IPF patients. Investigations of its clinical value in monitoring disease progression and treatment response are needed in the future.

Environmental Exposures, Characteristics, and Treatment Outcomes of Hypersensitivity Pneumonitis at a Rural Appalachian Academic Medical Center: A Cross-sectional Study

Purpose: Hypersensitivity pneumonitis (HP) is a form of interstitial lung disease (ILD) caused by inhalational exposure to an antigen. Little is known about the exposures, outcomes, and management of HP in rural Appalachian patients. Methods: A retrospective cross-sectional study was conducted from January 1, 2017, to June 30, 2022, at a tertiary academic medical center. Sixty-two patients were initially screened, and seven patients fulfilled the inclusion criteria. The primary outcome was the exposure leading to HP. Secondary outcomes included the disease stage at diagnosis, smoking rate, treatment modalities, ILD exacerbation rate, and mortality. Results: Birds and mold are the more common exposures attributed to HP (both n=2, 28.57%). Novel exposures to continuous positive airway pressure devices, vapor and/or fumes, and fiberglass were noted (each n=1, 14.28%). Three patients (42.85%) had fibrotic HP at presentation. Most patients were ever-smokers (n=4, 57.14%). All patients (n=7, 100%) received corticosteroids with a mean duration of use of 2.50 ± 0.65 months, and a mean dose of 37.14 ± 12.54 mg. One (14%) patient was compliant with antigen elimination. ILD exacerbation and mortality rate was high (both n=2, 28.57%). Conclusion: The exposures identified in rural Appalachian HP patients were similar to other rural and urban populations in the United States. Risk factors associated with poor outcomes, such as smoking, fibrotic HP subtype, and non-avoidance of antigen were higher in this cohort. The rate of ILD exacerbation and mortality were similarly higher. Larger studies are needed to investigate longitudinal trends of exposure, characteristics, and management of HP to improve outcomes in rural populations.

A rare case of childhood interstitial lung disease attributed to desquamative interstitial pneumonia

Desquamative interstitial pneumonia (DIP) is a rare form of interstitial lung disease (ILD) in children that can be idiopathic but is usually associated with an inborn error of surfactant metabolism. We reported DIP in a 13-year-old girl who was referred to our outpatient clinic because of worsening dyspnea. High-resolution computed tomography showed ground-glass attenuation with honeycombing and intralobular, interstitial septal thickening, suggestive of an ILD. Transbronchial lung biopsy was performed, and histopathology findings were consistent with DIP. The patient was started on steroid therapy with oxygen support. Unfortunately, she died a month after being diagnosed due to disease progression.

Anti-Inflammatory and Antifibrotic Potential of Longidaze in Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Hypomorphic pathogenic variant in SFTPB leads to adult pulmonary fibrosis.

Biallelic pathogenic variants in the surfactant protein (SP)-B gene (SFTPB) have been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We herein report the cases of two related adults with pulmonary fibrosis due to a new homozygous SFTPB pathogenic variant, c.582G>A p.(Gln194=). In vitro transcript studies showed that this SFTPB synonymous pathogenic variant induces aberrant splicing leading to three abnormal transcripts with the preservation of the expression of a small proportion of normal SFTPB transcripts. Immunostainings on lung biopsies of the proband showed an almost complete loss of SP-B expression. This hypomorphic splice variant has thus probably allowed the patients' survival to adulthood while inducing an epithelial cell dysfunction leading to ILD. Altogether, this report shows that SFTPB pathogenic variants should be considered in atypical presentations and/or early-onset forms of ILD particularly when a family history is identified.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Expanded T regulatory cells fail to control germinal center responses in the lung lymph nodes of pulmonary fibrosis patients

Abstract Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung diseases (ILD), which is characterized by progressive scarring of the lung. While immune suppression is a viable therapeutic option for many ILDs, it is detrimental in IPF. Nevertheless, enlargement of lung-draining lymph nodes (LLN) is prevalent and predicts survival outcomes in all ILD patients, including IPF, suggesting that there is also an immune component to IPF pathogenesis. To test this hypothesis, we investigated the cellular composition of the LLN in IPF and non-IPF ILD patients. All ILD patients’ LLN had increased germinal centers (GC), implicating that immune responses are not being resolved. As T regulatory cells (Tregs) are key in the control and resolution of immune responses, we investigated the phenotype of Tregs in the LLN of both IPF and non-IPF ILD patients to reveal their role in lung fibrosis. Tregs were expanded in LLN of all ILD patients compared to controls. Interestingly, there was a predominance of GATA3-expressing Tregs in ILD patients’ LLN. However, Tregs of ILD patients expressed significantly elevated levels of ICOS and CD137 compared to controls, indicating recent activation. Surprisingly, CD25 expression was significantly lower on Tregs from ILD patients’ LLN. Sc-RNAseq confirms similar Treg phenotypes in the lungs of IPF patients. In a mouse model of bleomycin-induced pulmonary fibrosis, Tregs expand and display a similar activated phenotype. Preliminary experiments suggest that GATA3 expression in Tregs is detrimental in this model. Together, these data indicate that there are unresolved GC responses in the LLN of all ILD patients, including IPF, and suggest that Tregs are ineffectual at controlling the GC response. American Heart Association Postdoctoral Fellowship, Award number (835938)

The role of radiological research methods in the diagnosis of rare forms of interstitial lung diseases in newborns

Introduction. Interstitial lung diseases in newborns associated with diffuse pulmonary developmental disorders are a difficult to detect, as they are rare, formed at the early stages of embryonic development, clinically manifested in the first hours of life as severe respiratory distress syndrome in newborns. The aim. To demonstrate the role of radiation research methods and the difficulties of differential diagnosis of rare forms of interstitial lung diseases associated with diffuse impaired lung development. Materials and methods. Clinical cases of congenital alveolar dysplasia and alveolar-capillary dysplasia with an abnormal location of the pulmonary veins are described in detail, the radiological data, confirmed by the histological data, are presented. Results. Specific changes in the lungs in ILD of newborns associated with a diffuse disorder of lung development, according to X-ray data in the first day of life, are not determined, however, a progressive negative trend has been noted. The lungs computed tomography allows a detailed diagnosis of structural changes in the lung parenchyma, their severity and prevalence. Issues of differential diagnosis of diffuse disorders of lung development in newborns are discussed; the obtained results correlate with the published data. Conclusions. Histological examination is the “gold standard” in the diagnosis of interstitial lung diseases associated with diffuse lung developmental disorders in newborns, but is most often performed at autopsy. The role of radiological methods in the algorithmic approach of diagnostics is increasing due to the accumulated data, the improvement in the quality of detection and recognition of rare variants of interstitial lung diseases in newborns according to CT of the chest organs.

ORGANIZING PNEUMONIA: AN UNUSUAL SEQUELA OF COVID-19 INFECTION.

COVID-19 pneumonia is one of the secondary causes of organizing pneumonia (OP).Early initiation of steroids in OP is associated with improvement in symptoms and prognosis.A prolonged course of steroids may be needed in COVID-induced OP.

GROUND GLASS OPACITIES: SIGN OF CAUTION IN TYPICAL INTERSTITIAL PNEUMONIA

Typical interstitial pneumonia (IP) is mainly the fibrotic form of interstitial lung disease. In some cases with typical IP, a certain amount of ground-glass opacity (GGO) can be detected on high-resolution computed tomography, however, some important issues, such as the co-existence of GGO and typical IP, still require further investigation by biopsy. After the diagnosis of typical IP, anti-fibrosis treatment is usually considered. Here, we hypothesized that GGO in typical IP could be a manifestation of an acute inflammatory attack requiring immunosuppressive therapy or an indicator of ongoing contact with trigger factors that initiate pathological reactions in typical IP.

Pleuroparenchymal Fibroelastosis following Asbestos Exposure

Background: Pleuroparenchymal fibroelastosis is considered a rare form of interstitial lung disease. There are a growing number of case reports, however no large-scale studies detailing both clinical and histopathological features along with long term follow-up. An association with asbestos exposure has been described however this too has been limited to a few case reports. Case Report: A 73-year-old man with a history of interstitial lung disease and asbestos exposure presented with dyspnea with biopsy and imaging suggestive of pleuroparenchymal fibroelastosis. Despite steroid and anti-fibrotic therapy, the disease advanced rapidly causing the patient and family to pursue palliative care. Conclusion: Asbestos exposure is a significant risk factor for pleuroparenchymal fibroelastosis, a rare but increasingly recognized entity. Biopsy and image findings are the mainstay of diagnosis, pulmonary function tests are useful in prognostication. Treatment is supportive.

Role of Circular RNAs in Pulmonary Fibrosis.

Pulmonary fibrosis is a chronic progressive form of interstitial lung disease, characterized by the histopathological pattern of usual interstitial pneumonia. Apart from aberrant alterations of protein-coding genes, dysregulation of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs (circRNAs), is crucial to the initiation and progression of pulmonary fibrosis. CircRNAs are single-stranded RNAs that form covalently closed loops without 5′ caps and 3′ tails. Different from canonical splicing of mRNA, they are produced from the back-splicing of precursor mRNAs and have unique biological functions, as well as potential biomedical implications. They function as important gene regulators through multiple actions, including sponging microRNAs and proteins, regulating transcription, and splicing, as well as protein-coding and translation in a cap-independent manner. This review comprehensively summarizes the alteration and functional role of circRNAs in pulmonary fibrosis, with a focus on the involvement of the circRNA in the context of cell-specific pathophysiology. In addition, we discuss the diagnostic and therapeutic potential of targeting circRNA and their regulatory pathway mediators, which may facilitate the translation of recent advances from bench to bedside in the future.